Fundamental studies in the chemistry of natural products with emphasis on synthesis, and including extension of the basic theoretical background for the design and understanding of chemical reactions. In the vitamin B12 area it is anticipated that the preparation of a reference sample of totally synthetic vitamin B12 will be completed. It is hoped that superior methods may be developed for the elaboration of the characteristic large vitamin B12 side chain. The removal of the cobalt atom from vitamin B12 will be attempted, with a view to making detailed studies of the metal-free substance, and vitamin B12 analogs with other metals. Major effort will be devoted to the further extensions of work on macrolide synthesis with erythromycin as the first major objective. Work is projected on the synthesis of homopolynucleotides and bicyclomycin. It is quite possible that our work will encompass studies of the synthesis of other non-macromolecular substances of biological and medical interest.